GWAS analyses have identified several genetic loci with statistically robust and reproducible SNP/indel associations, cementing the polygenic nature of addiction. However, with only a fraction of the heritability explained (for example, 15% of the variance in nicotine dependence [121] and 13% of the variance in alcohol consumption [58] explained by common SNPs together) and limited knowledge of the neurobiological pathways leading to addiction, much remains to be discovered. We fully expect that GWAS analyses conducted with sample sizes into the hundreds of thousands and millions will replicate previously suggested, but currently unreplicated, genetic variants and will also unveil novel variants. As evidenced by the GWAS-identified variants identified to date (mainly SNPs), novel variants will likely exert small effect sizes on developing addiction but potentially uncover previously unrecognized neurobiological pathways. Additional heritability may also be explained by complex interactions of genetic variants with one another and with prominent environmental exposures, which will likely require very large sample sizes with harmonized exposures and addiction phenotypes across multiple datasets. In the future expansion of GWAS sample sizes, we emphasize the importance of including
